1. PJ Devereaux, Population Health Research Institute, Hamilton, Canada on behalf of POISE-2 Investigators PeriOperative ISchemic Evaluation-2 Trial POISE-2POISE-2 Aspirin in patients undergoing noncardiac surgery

2. Background Worldwide 200 million adults undergo noncardiac surgery annually 10 million suffer major vascular complication MI is most common Surgery – associated with platelet activation thrombosis may be mechanism of periop MI

3. Background Strong evidence aspirin prevents periop VTE but physicians more commonly use anticoagulants Substantial variability in periop usage of aspirin aspirin-naive patients and patients taking aspirin chronically

4. Methods Design – blinded 2 X 2 factorial RCT aspirin vs placebo clonidine vs placebo Eligibility criteria – undergoing noncardiac surgery, ≥45 yrs, at risk of vascular complication Excluded patients BMS <6 weeks before surgery DES <1 year before surgery took aspirin within 72 hrs before surgery

5. Methods 2 aspirin strata Initiation Stratum (n=5628) Continuation Stratum (n=4382) Intervention aspirin/placebo (200 mg) just before surgery; continued daily (100 mg) 30 days in Initiation Stratum and 7 days in Continuation Stratum Primary outcome death or nonfatal MI at 30 days

6. Outcome definitions MI – universal definition of MI Life threatening bleed – bleeding event with –emergent surgery, intracranial hemorrhage, –hypotension required inotrope or vasopressor, or –fatal outcome Major bleed – bleeding with –Hb ≤70 g/L and ≥2 units RBCs; –Hb drop ≥50 g/L and ≥2 units of RBCs; –≥4 units of RBCs within 24 hr period; –intervention (e.g., embolization); or –retroperitoneal, intraspinal, or intraocular bleed

7. Recruitment by region Follow-up complete on 99.9% of patients

8. Preoperative characteristics CharacteristicsAspirin (N=4998) Placebo (N=5012) Age – (mean yrs)68.6 Male (%)52.053.6 Known vascular disease 32.732.6 History of PCI4.7

9. Type of surgery and periop anticoagulant prophylaxis SurgeryAspirin (N=4998) Placebo (N=5012) Orthopedic General Urologic or gynecologic Vascular Other 38.2 26.8 16.7 6.2 12.1 39.2 26.8 16.8 5.9 11.3 65% of patients received prophylactic anticoagulant

10. 1 O and 2 O outcome results OutcomeAspirin (4998) Placebo (5012) HR (95% CI) P 1 O outcome: death or nonfatal MI 351 (7.0)355 (7.1)0.99 (0.86-1.15)0.92 2 O outcomes: death, MI, or stroke 362 (7.2)370 (7.4)0.98 (0.85-1.13)0.80 death, MI, revasc, PE, DVT 402 (8.0)407 (8.1)0.99 (0.86-1.14)0.90 No interaction with clonidine study drug

11. Tertiary outcome results OutcomeAspirin (4998) Placebo (5012) HR (95% CI) P Mortality65 (1.3)62 (1.2)1.05 (0.74-1.49)0.78 MI309 (6.2)315 (6.3)0.98 (0.84-1.15)0.85 Periph arterial thrombosis 13 (0.3)15 (0.3) 0.87 (0.41-1.83) 0.71

12. Tertiary outcome results OutcomeAspirin (4998) Placebo (5012) HR (95% CI) P Mortality65 (1.3)62 (1.2)1.05 (0.74-1.49)0.78 MI309 (6.2)315 (6.3)0.98 (0.84-1.15)0.85 Periph arterial thrombosis 13 (0.3)15 (0.3) 0.87 (0.41-1.83) 0.71 PE33 (0.7)31 (0.6)1.07 (0.65-1.74)0.79 DVT25 (0.5)35 (0.7)0.72 (0.43-1.20)0.20 acute kidney injury, dialysis 33 (0.7)19 (0.4) 1.75 (1.00-3.09) 0.05

13. Safety outcome results OutcomeAspirin (4998) Placebo (5012) HR (95% CI) P Major bleed 229 (4.6)187 (3.7) 1.23 (1.01-1.49) 0.04 Life-threat bleed 87 (1.7)73 (1.5) 1.19 (0.88-1.63) 0.26 Stroke 16 (0.3)19 (0.4) 0.84 (0.43-1.64) 0.62

14. Strata and bleeding results Primary and 2 nd outcome results similar in both aspirin strata Multivariable regression – life-threatening or major bleed independent predictor of periop MI –HR, 1.82; (95% CI, 1.40-2.36); P<0.001

15. Conclusions Periop aspirin did not prevent death or MI but increased risk of major bleeding findings apply to both patients naive to aspirin and patients taking aspirin chronically Life-threatening and major bleeding independent predictor of MI may explain difference b/w non-operative & periop aspirin results